Regulation of Nrf2- and AP-l-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells

Aim： To examine the regulatory crosstalk between the transcription factors Nrf2 and AP-1 in prostate cancer （Pea） by dietary cancer chemopreventive compounds （-）epigallocatechin-3-gallate （EGCG） from green tea and sulforaphane （SFN） from cruciferous vegetables. Methods： We performed （i） in vitro stu...

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Published in:Acta pharmacologica Sinica 2010 (9), p.1223-1240
Main Author: Sujit NAIR Avantika BARVE Tin-Oo KHOR Guo-xiang SHEN Wen LIN Jefferson Y CHAN Li CAI Ah-Ng KONG
Format: Article
Language:English
Subjects:
PCR技术
前列腺癌细胞
基因敲除
基因表达调控
没食子酸
转录因子结合位点
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Summary:Aim： To examine the regulatory crosstalk between the transcription factors Nrf2 and AP-1 in prostate cancer （Pea） by dietary cancer chemopreventive compounds （-）epigallocatechin-3-gallate （EGCG） from green tea and sulforaphane （SFN） from cruciferous vegetables. Methods： We performed （i） in vitro studies including luciferase reporter gene assays, MTS cell viability assays, and quantitative real- time PCR （qRT-PCR） in PC-3 AP-1 human PCa cells, （ii） in vivo temporal （3 h and 12 h） microarray studies in the prostate of Nrf2-deficient mice that was validated by qRT-PCR, and （iii） in silico bioinformatic analyses to delineate conserved Transcription Factor Binding Sites （TFBS） in the promoter regions of Nrf2 and AP-1, as well as coregulated genes including ATF-2 and ELK-I. Results： Our study shows that AP-1 activation was attenuated by the combinations of SFN （25 μmol/L） and EGCG （20 or 100 μmol/L） in PC-3 cells. Several key Nrf2-dependent genes were down-regulated （3-fold to 35-fold） after in vivo administration of the combination of EGCG （100 mg/kg） and SFN （45 mg/kg）. Conserved TFBS signatures were identified in the promoter regions of Nrf2, AP-1, ATF2, and ELK-1 suggesting a potential regulatory mechanism of crosstalk between them. Conclusion： Taken together, our present study of transcriptome profiling the gene expression changes induced by dietary phytochemicals SFN and EGCG in Nrf2-deficient mice and in PC-3 cells in vitro demonstrates that the effects of SFN＋EGCG could be mediated via concerted modulation of Nrf2 and AP-1 pathways in the prostate.
ISSN:1671-4083
1745-7254